Hyaluronic acid-functionalized Fe₃O₄ nanoparticles loaded with trans-chalcone: in vitro anticancer activity and lncRNA modulation in hepatocellular carcinoma cells.

Authors

Maryam Daghari, Ali Salehzadeh, Afshin Pourahmad, Reza Yari

Published in

Scientific reports. Jul 04, 2026. Epub Jul 04, 2026.

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Targeting cancer cells using functionalized nanoparticles has gained attention. In this study, the anticancer potential of Iron oxide NPs functionalized with Glucose and co-conjugated with Hyaluronic acid and trans-Chalcone (Fe₃O₄@Glu-HA-TC NPs) and their influence on the expression of the lncRNAs ANRIL and ANCR was investigated. The synthesized NPs were characterized by FT-IR, XRD, SEM, EDS, DLS, zeta potential, TGA and VSM analysis. Viability level of the HepG2 and HDF cell lines was studied by MTT assay and cell cycle phases and apoptosis/necrosis percentage and ROS levels in the HepG2 cell treated with Fe₃O₄@Glu-HA-TC NPs were determined. Relative expression of the lncRNAs ANCR and ANRIL was determined by Real-Time PCR assay. The NPs were spherical, moderately agglomerated, with an average particle diameter of 42.05 nm, surface charge of -56.8 mV, hydrodynamic size of 150.9 nm and saturated magnetization at 38.88 emu/g. Fe₃O₄@Glu-HA-TC NPs exhibited greater cytotoxicity toward HepG2 cells compared to normal HDF cells with an IC₅₀ of 255 and 488.79 µg/mL, respectively. Exposure to the NPs caused an apparent blockage at the sub-G1 phase, notably elevated early and late apoptosis (as observed in a representative flow cytometry experiment), and induced ROS generation by approximately 3.4-fold. In addition, treatment with Fe₃O₄@Glu-HA-TC NPs significantly upregulated the lncRNA ANCR (1.52-fold) while slight downregulation the ANRIL (0.89-fold). The present work provides evidence that Fe₃O₄@Glu-HA-TC NPs induce cytotoxicity, cell cycle arrest, and apoptosis in HepG2 cells, with associated ROS generation and lncRNA expression changes. However, mechanistic validation (e.g., antioxidant rescue, lncRNA functional assays) is needed to establish causality. It should be noted that while hyaluronic acid functionalization was employed as a rationale for potential CD44-mediated uptake, direct evidence of receptor-mediated targeting was not obtained in this study.

PMID:
42401688
Bibliographic data and abstract were imported from PubMed on 05 Jul 2026.

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